The link between obesity and insulin resistance largely accounts for the pathogenesis of metabolic syndrome and diabetes mellitus, in which adipokine expression plays a key role. Puerarin, a major active isoflavone extracted from the traditional Chinese medicine Radix Puerariae, has been studied for its comprehensive biological actions. However, its effect on high-fat diet (HFD)-induced insulin resistance and adipokine expression in rat has not been well investigated. In the present study, male Sprague–Dawley rats were fed on a normal control diet (NCD) or HFD for 6 weeks, followed by administration of puerarin (100 and 200 mg/kg) for up to 8 weeks. Compared to NCD, HFD feeding for 6 weeks led to increased body weight gain and impaired glucose/insulin tolerance manifested by oral glucose/intraperitoneal insulin tolerance tests in rats. These exacerbations prolonged through HFD feeding, but were effectively reversed by puerarin administration. Enzyme-linked immunosorbent assay demonstrated that, serum levels of leptin and resistin, but not that of adiponectin, were markedly augmented by HFD and retarded by puerarin treatment. Real-time reverse transcription polymerase chain reaction results showed that, in agreement with the circulating levels, mRNA expression of leptin and resistin in epididymal white adipose tissue was modified by HFD and improved by puerarin in the same pattern. Collectively, we revealed that puerarin could improve body weight gain, glucose/insulin intolerance and adipokine expression in HFD-induced insulin resistant rats, indicating its potential value for treatment of metabolic syndrome.